Nancy Abu-Bonsrah

Local delivery methods of therapeutic agents in the treatment of diffuse intrinsic brainstem gliomas

Brainstem gliomas comprise 10-20% of all pediatric central nervous system (CNS) tumors and diffuse intrinsic pontine gliomas (DIPGs) account for the majority of these lesions. DIPG is a rapidly progressive disease with almost universally fatal outcomes and a median survival less than 12 months. Current standard-of-care treatment for DIPG includes radiation therapy, but its long-term survival effects are still under debate. Clinical trials investigating the efficacy of systemic administration of various therapeutic agents have been associated with disappointing outcomes. Recent efforts have focused on improvements in chemotherapeutic agents employed and in methods of localized and targeted drug delivery. This review provides an update on current preclinical and clinical studies investigating treatment options for brainstem gliomas.

The epidemiology of spinal tuberculosis in the United States: an analysis of 2002–2011 data

OBJECTIVE The aim of this study was to investigate the incidence of spinal tuberculosis (TB) in the US between 2002 and 2011. METHODS The Nationwide Inpatient Sample database from 2002 to 2011 was used to identify patients with a discharge diagnosis of TB and spinal TB. Demographic and hospital data were obtained for all admissions, and included age, sex, race, comorbid conditions, insurance status, hospital location, hospital teaching status, and hospital region. The incidence rate of spinal TB adjusted for population growth was calculated after application of discharge weights. RESULTS A total of 75,858 patients with a diagnosis of TB were identified, of whom 2789 had a diagnosis of spinal TB (3.7%); this represents an average of 278.9 cases per year between 2002 and 2011. The incidence of spinal TB decreased significantly-from 0.07 cases per 100,000 persons in 2002 to 0.05 cases per 100,000 in 2011 (p < 0.001), corresponding to 1 case per 2 million persons in the latter year. The median age for patients with spinal TB was 51 years, and 61% were male; 11.6% were patients with diabetes, 11.4% reported recent weight loss, and 8.1% presented with paralysis. There were 619 patients who underwent spinal surgery for TB, with the most common location being the thoracolumbar spine (61.9% of cases); 50% of patients had instrumentation of 3 or more spinal segments. CONCLUSIONS During the examined 10-year period, the incidence of spinal TB was found to significantly decrease over time in the US, reaching a rate of 1 case per 2 million persons in 2011. However, the absolute reduction was relatively small, suggesting that although it is uncommon, spinal TB remains a public health concern and most commonly affects male patients approximately 50 years of age. Approximately 20% of patients with spinal TB underwent surgery, most commonly in the thoracolumbar spine.

The Impact of Smoking on 30-day Morbidity and Mortality in Adult Spinal Deformity Surgery.

Study Design. A retrospective cohort study of a prospectively collected surgical database. Objective. The aim of this study was to investigate the effect of smoking on 30-day morbidity and mortality in patients undergoing surgery for adult spinal deformity (ASD). Summary of Background Data. There is conflicting evidence regarding the impact of smoking on short-term outcomes after spinal fusion. Methods. A retrospective review of the prospectively collected American College of Surgeons National Surgical Quality Improvement database was performed for the years 2007 to 2013. Patients who underwent spinal fusion for ASD were identified. Thirty-day morbidity and mortality were compared between current smokers and nonsmokers. The independent effect of smoking was investigated via multivariate logistic regression analysis. Results. A total of 1368 patients met inclusion criteria and were included in this study. Of the 1368 patients, 15.9% were smokers and 84.1% nonsmokers. The proportion of smokers who developed at least one complication was 9.7% versus 13.6% for nonsmokers (P = 0.119). Major complication rates (including 30-day mortality) were 6.5% for smokers and 8.4% for nonsmokers (P = 0.328). Current smoking status was not associated with increased odds of developing any complication [odds ratio (OR) 0.90; 95% confidence interval (95% CI), 0.47–1.71; P = 0.752] or major complications (OR 1.32; 95% CI 0.64–2.70; P = 0.447) after multivariate analysis. Conclusion. Smoking was not associated with higher 30-day complications or mortality after corrective surgery for ASD in this study. However, given the negative effects of smoking on overall health and spine surgery outcomes in the long term, smoking cessation before spinal fusion is still recommended. Level of Evidence: 3

Efficacy of primary microvascular decompression versus subsequent microvascular decompression for trigeminal neuralgia.

OBJECTIVE Trigeminal neuralgia (TN) is characterized by intermittent, paroxysmal, and lancinating pain along the distribution of the trigeminal nerve. Microvascular decompression (MVD) directly addresses compression of the trigeminal nerve. The purpose of this study was to determine whether patients undergoing MVD as their first surgical intervention experience greater pain control than patients who undergo subsequent MVD. METHODS A retrospective review of patient records from 1998 to 2015 identified a total of 942 patients with TN and 500 patients who underwent MVD. After excluding several cases, 306 patients underwent MVD as their first surgical intervention and 175 patients underwent subsequent MVD. Demographics and clinicopathological data and outcomes were obtained for analysis. RESULTS In patients who underwent subsequent MVD, surgical intervention was performed at an older age (55.22 vs 49.98 years old, p < 0.0001) and the duration of symptoms was greater (7.22 vs 4.45 years, p < 0.0001) than for patients in whom MVD was their first surgical intervention. Patients who underwent initial MVD had improved pain relief and no improvement in pain rates compared with those who had subsequent MVD (95.8% and 4.2% vs 90.3% and 9.7%, respectively, p = 0.0041). Patients who underwent initial MVD had significantly lower rates of facial numbness in the pre- and postoperative periods compared with patients who underwent subsequent MVD (p < 0.0001). The number of complications in both groups was similar (p = 0.4572). CONCLUSIONS The results demonstrate that patients who underwent other procedures prior to MVD had less pain relief and a higher incidence of facial numbness despite rates of complications similar to patients who underwent MVD as their first surgical intervention.

A Systematic Review of Metastatic Hepatocellular Carcinoma to the Spine

BACKGROUND Hepatocellular carcinoma (HCC) frequently metastasizes to the spine. The impact of medical and/or surgical intervention on overall survival has been examined in a limited number of clinical studies, and herein we systematically review these data. METHODS We performed a literature review using PubMed, Embase, CINAHL, and Web of Science to identify articles that reported survival, clinical outcomes, and/or prognostic factors associated with patients diagnosed with spinal metastases. The methodologic quality of each review was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses tool. RESULTS There were 26 articles (152 patients) that met the inclusion criteria and were treated with either surgery, radiotherapy, chemotherapy, and/or observation. There were 3 retrospective cohort studies, 17 case reports, 5 case series, and 1 longitudinal observational study. Of the patients with known overall survival after diagnosis of spinal metastasis, survival at 3 months, 6 months, 1 year, 2 years, and 5 years was 95.2%, 83.0%, 28.6%, 2.0%, and 1.4%, respectively. The median survival after diagnosis of the metastasis was 0.7 months in the patients who received no treatment, 7 months in the patients treated with surgical intervention alone, 6 months for patients who received chemotherapy and/or radiation, and 13.5 months in the patients treated with a combination of surgery and medical management. All other clinical or prognostic parameters were of low or insufficient strength. CONCLUSIONS Patients diagnosed with HCC spinal metastasis have a 10.6-month overall survival. Further analysis of patients in prospective controlled trials will be essential to the development of treatment algorithms for these patients in the future.

Extraneural Glioblastoma Multiforme Vertebral Metastasis

Glioblastoma multiforme (GBM) is the most common malignant central nervous system tumor; however, extraneural metastasis is uncommon. Of those that metastasize extraneurally, metastases to the vertebral bodies represent a significant proportion. We present a review of 28 cases from the published literature of GBM metastasis to the vertebra. The mean age at presentation was 38.4 years with an average overall survival of 26 months. Patients were either asymptomatic with metastasis discovered at autopsy or presented with varying degrees of pain, weakness of the extremities, or other neurologic deficits. Of the cases that included the time to spinal metastasis, the average time was 26.4 months with a reported survival of 10 months after diagnosis of vertebral metastasis. A significant number of patients had no treatments for their spinal metastasis, although the intracranial lesions were treated extensively with surgery and/or adjuvant therapy. With increasing incremental gains in the survival of patients with GBM, clinicians will encounter patients with extracranial metastasis. As such, this review presents timely information concerning the presentation and outcomes of patients with vertebral metastasis.

Factors associated with improved survival following surgery for renal cell carcinoma spinal metastases

OBJECTIVE Renal cell carcinoma (RCC) frequently metastasizes to the spine, causing pain or neurological dysfunction, and is often resistant to standard therapies. Spinal surgery is frequently required, but may result in high morbidity rates. The authors sought to identify prognostic factors and determine clinical outcomes in patients undergoing surgery for RCC spinal metastases. METHODS The authors searched the records of patients who had undergone spinal surgery for metastatic disease at a single institution during a 12-year period and retrieved data for 30 patients with metastatic RCC. The records were retrospectively reviewed for data on preoperative conditions, treatment, and survival. Statistical analyses (i.e., Kaplan-Meier survival analysis and log-rank test in univariate analysis) were performed with R version 2.15.2. RESULTS The 30 patients (23 men and 7 women with a mean age of 57.6 years [range 29-79 years]) had in total 40 spinal surgeries for metastatic RCC. The indications for surgery included pain (70%) and weakness (30%). Fourteen patients (47%) had a Spinal Instability Neoplastic Score (SINS) indicating indeterminate or impending instability, and 6 patients (20%) had a SINS denoting instability. The median length of postoperative survival estimated with Kaplan-Meier analysis was 11.4 months. Younger age (p = 0.001) and disease control at the primary site (p = 0.005), were both significantly associated with improved survival. In contrast, visceral (p = 0.002) and osseous (p = 0.009) metastases, nonambulatory status (p = 0.001), and major comorbidities (p = 0.015) were all significantly associated with decreased survival. Postoperative Frankel grades were the same or had improved in 78% of patients. Major complications occurred in 9 patients, and there were 3 deaths (10%) during the 30-day in-hospital period. Three en bloc resections were performed. CONCLUSIONS Resection and fixation may provide pain relief and neurological stabilization in patients with spinal metastases arising from RCC, but surgical morbidity rates remain high. Younger patients with solitary spinal metastases, good neurological function, and limited major comorbidities may have longer survival and may benefit from aggressive intervention.

The Afro-Cardiac Study: Cardiovascular Disease Risk and Acculturation in West African Immigrants in the United States: Rationale and Study Design.

Cardiovascular disease (CVD) remains the leading cause of death in the United States (US). African-descent populations bear a disproportionate burden of CVD risk factors. With the increase in the number of West African immigrants (WAIs) to the US over the past decades, it is imperative to specifically study this new and substantial subset of the African-descent population and how acculturation impacts their CVD risk. The Afro-Cardiac study, a community-based cross-sectional study of adult WAIs in the Baltimore–Washington metropolis. Guided by the PRECEDE–PROCEED model, we used a modification of the World Health Organization Steps survey to collect data on demographics, socioeconomic status, migration-related factors and behaviors. We obtained physical, biochemical, acculturation measurements as well as a socio-demographic and health history. Our study provides critical data on the CVD risk of WAIs. The framework used is valuable for future epidemiological studies addressing CVD risk and acculturation among immigrants.

Percutaneous embolization and spondylectomy of an aggressive L2 hemangioma.

Spinal hemangiomas are commonly benign primary tumors of the spine that can result in pathologic vertebral fractures or spinal cord compression with neurologic deficit [1–3]. A 68-year-old woman presented with an L2 lesion that was discovered during workup of abdominal and lumbosacral pain. The radiological appearance was consistent with hemangioma demonstrating a T1 hypointense and T2 hyperintense expansile and lytic lesion (Fig. 1B, F, D, H) confirmed by percutaneous transpedicular biopsy. A spinal angiogram was done, but arterial embolization was avoided because of concern for distal flow to the anterior spinal artery. Therefore, direct administration of n-butyl cyanoacrylate was delivered to the tumor percutaneously via a transpedicular route (Fig. 1C, G). Two days after percutaneous embolization, the patient underwent spondylectomy of L2 vertebrae from a posterior approach with reconstruction (Fig. 2A, B).

Molecular Markers and Targeted Therapeutics in Metastatic Tumors of the Spine: Changing the Treatment Paradigms.

Study Type. A review of the literature. Objective. The aim of this study was to discuss the evolution of molecular signatures and the history and development of targeted therapeutics in metastatic tumor types affecting the spinal column. Summary of Background Data. Molecular characterization of metastatic spine tumors is expected to usher in a revolution in diagnostic and treatment paradigms. Molecular characterization will provide critical information that can be used for initial diagnosis, prognosticating the ideal treatment strategy, assessment of treatment efficacy, surveillance and monitoring recurrence, and predicting complications, clinical outcome, and overall survival in patients diagnosed with metastatic cancers to the spinal column. Methods. A review of the literature was performed focusing on illustrative examples of the role that molecular-based therapeutics have played in clinical outcomes for patients diagnosed with metastatic tumor types affecting the spinal column. Results. The impact of molecular therapeutics including receptor tyrosine kinases and immune checkpoint inhibitors and the ability of molecular signatures to provide prognostic information are discussed in metastatic breast cancer, lung cancer, prostate cancer, melanoma, and renal cell cancer affecting the spinal column. Conclusion. For the providers who will ultimately counsel patients diagnosed with metastases to the spinal column, molecular advancements will radically alter the management/surgical paradigms utilized. Ultimately, the translation of these molecular advancements into routine clinical care will greatly improve the quality and quantity of life for patients diagnosed with spinal malignancies and provide better overall outcomes and counseling for treating physicians. Level of Evidence: N/A